scholarly journals Post-antifungal effect of amphotericin B and voriconazole against germinated Aspergillus fumigatus conidia

2008 ◽  
Vol 61 (6) ◽  
pp. 1309-1311 ◽  
Author(s):  
E. Chryssanthou ◽  
A. Loebig ◽  
J. Sjolin
Keyword(s):  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Antifungal Effect

scholarly journals Dectin-2-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Suresh Ambati ◽  
Emma C. Ellis ◽  
Jianfeng Lin ◽  
Xiaorong Lin ◽  
Zachary A. Lewis ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Effective Dose ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Antifungal Drugs ◽  
Extracellular Matrices ◽  
Content Type ◽  
Order Of Magnitude ◽  
Life Threatening

ABSTRACT Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus cause life-threatening candidiasis, cryptococcosis, and aspergillosis, resulting in several hundred thousand deaths annually. The patients at the greatest risk of developing these life-threatening invasive fungal infections have weakened immune systems. The vulnerable population is increasing due to rising numbers of immunocompromised individuals as a result of HIV infection or immunosuppressed individuals receiving anticancer therapies and/or stem cell or organ transplants. While patients are treated with antifungals such as amphotericin B, all antifungals have serious limitations due to lack of sufficient fungicidal effect and/or host toxicity. Even with treatment, 1-year survival rates are low. We explored methods of increasing drug effectiveness by designing fungicide-loaded liposomes specifically targeted to fungal cells. Most pathogenic fungi are encased in cell walls and exopolysaccharide matrices rich in mannans. Dectin-2 is a mammalian innate immune membrane receptor that binds as a dimer to mannans and signals fungal infection. We coated amphotericin-loaded liposomes with monomers of Dectin-2’s mannan-binding domain, sDectin-2. sDectin monomers were free to float in the lipid membrane and form dimers that bind mannan substrates. sDectin-2-coated liposomes bound orders of magnitude more efficiently to the extracellular matrices of several developmental stages of C. albicans, C. neoformans, and A. fumigatus than untargeted control liposomes. Dectin-2-coated amphotericin B-loaded liposomes reduced the growth and viability of all three species more than an order of magnitude more efficiently than untargeted control liposomes and dramatically decreased the effective dose. Future efforts focus on examining pan-antifungal targeted liposomal drugs in animal models of fungal diseases. IMPORTANCE Invasive fungal diseases caused by Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus have mortality rates ranging from 10 to 95%. Individual patient costs may exceed $100,000 in the United States. All antifungals in current use have serious limitations due to host toxicity and/or insufficient fungal cell killing that results in recurrent infections. Few new antifungal drugs have been introduced in the last 2 decades. Hence, there is a critical need for improved antifungal therapeutics. By targeting antifungal-loaded liposomes to α-mannans in the extracellular matrices secreted by these fungi, we dramatically reduced the effective dose of drug. Dectin-2-coated liposomes loaded with amphotericin B bound 50- to 150-fold more strongly to C. albicans, C. neoformans, and A. fumigatus than untargeted liposomes and killed these fungi more than an order of magnitude more efficiently. Targeting drug-loaded liposomes specifically to fungal cells has the potential to greatly enhance the efficacy of most antifungal drugs.

scholarly journals Potentiation of antifungal effect of amphotericin B by squalene, an intermediate for sterol biosynthesis.

1982 ◽  
Vol 35 (2) ◽  
pp. 230-234 ◽  
Author(s):  
AKINORI MASUDA ◽  
SHIN-ICHI AKIYAMA ◽  
MICHIHIKO KUWANO ◽  
NOBUO IKEKAWA
Keyword(s):  
Amphotericin B ◽  
Sterol Biosynthesis ◽  
Antifungal Effect

scholarly journals Black and white teas as potential agents to combine with amphotericin B and protect red blood cells from amphotericin B-mediated toxicity

2018 ◽  
Vol 78 (4) ◽  
pp. 673-678 ◽  
Author(s):  
V. M. Oliveira ◽  
N. M. Khalil ◽  
E. Carraro
Keyword(s):  
Side Effects ◽  
Red Blood Cells ◽  
Amphotericin B ◽  
Blood Cells ◽  
Fungal Infections ◽  
Black Tea ◽  
Additive Effects ◽  
Antifungal Effect ◽  
Black And White ◽  
Fungicidal Substance

Abstract Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.

Aspergillus terreus Species Complex

2021 ◽  
Author(s):  
Cornelia Lass-Flörl ◽  
Anna-Maria Dietl ◽  
Dimitrios P. Kontoyiannis ◽  
Matthias Brock
Keyword(s):  
At Risk ◽  
Aspergillus Fumigatus ◽  
Human Health ◽  
Amphotericin B ◽  
Species Complex ◽  
Aspergillus Terreus ◽  
Clinical Spectrum ◽  
Chronic Infections ◽  
Epidemiological Surveys ◽  
Risk Patients

Infections due to Aspergillus species are an acute threat to human health; members of the Aspergillus section Fumigati are the most frequently occurring agents, but depending on the local epidemiology, representatives of section Terrei or section Flavi are the second or third most important. Aspergillus terreus species complex is of great interest, as it is usually amphotericin B resistant and displays notable differences in immune interactions in comparison to Aspergillus fumigatus . The latest epidemiological surveys show an increased incidence of A. terreus as well as an expanding clinical spectrum (chronic infections) and new groups of at-risk patients being affected.

scholarly journals Dose Range Evaluation of Liposomal Nystatin and Comparisons with Amphotericin B and Amphotericin B Lipid Complex in Temporarily Neutropenic Mice Infected with an Isolate of Aspergillus fumigatus with Reduced Susceptibility to Amphotericin B

1999 ◽  
Vol 43 (11) ◽  
pp. 2592-2599 ◽  
Author(s):  
David W. Denning ◽  
Peter Warn
Keyword(s):  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Dose Range ◽  
Respiratory Arrest ◽  
Optimal Dosage ◽  
Lipid Complex ◽  
Amphotericin B Deoxycholate ◽  
Liver And Kidney ◽  
Amphotericin B Lipid Complex

ABSTRACT Using an isolate of Aspergillus fumigatus that is less susceptible in vivo to amphotericin B than most other isolates, we compared different doses of liposomal nystatin (L-nystatin), liposomal amphotericin B (L-amphotericin), and amphotericin B lipid complex (ABLC) with amphotericin B deoxycholate. Four experiments with intravenously infected neutropenic mice were conducted. A dose of L-nystatin at 10 mg/kg of body weight was toxic (the mice had fits or respiratory arrest). The optimal dosage of L-nystatin was 5 mg/kg daily on days 1, 2, 4, and 7 (90% survival). This was superior to L-amphotericin (5 mg/kg [P = 0.24] and 1 mg/kg [P < 0.0001]), ABLC (5 mg/kg [P = 0.014] and 1 mg/kg [P < 0.0001]), and amphotericin B deoxycholate (5 mg/kg [P = 0.008]). In terms of liver and kidney cultures, L-nystatin (5 mg/kg) was superior to all other regimens (P = 0.0032 and <0.0001, respectively). Higher doses of L-amphotericin (25 and 50 mg/kg) in one earlier experiment were more effective (100% survival) than 1 mg of L-amphotericin per kg and amphotericin deoxycholate (5 mg/kg) in terms of mortality and both liver and kidney culture results and to L-amphotericin (5 mg/kg) in terms of liver and kidney culture results only. ABLC (25 mg/kg) given daily for 7 days was superior to ABLC (50 mg/kg [P = 0.03]) but not to ABLC at 5 mg/kg or amphotericin B deoxycholate in terms of mortality, although it was in terms of liver and kidney culture results. No dose-response for amphotericin B (5 and 1 mg/kg) was demonstrable. In conclusion, in this stringent model, high doses of L-amphotericin and ABLC could overcome reduced susceptibility to amphotericin B deoxycholate, but all were inferior to 5- to 10-fold lower doses of L-nystatin.

scholarly journals Cerebral aspergillosis due to Aspergillus fumigatus in AIDS patient: first culture - proven case reported in Brazil

2005 ◽  
Vol 47 (3) ◽  
pp. 161-165 ◽  
Author(s):  
José E. Vidal ◽  
Rafi F. Dauar ◽  
Marcia S.C. Melhem ◽  
Walderez Szeszs ◽  
Sandra R.B.S. Pukinskas ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Brain Abscess ◽  
Brain Biopsy ◽  
Mass Effect ◽  
Aids Patients ◽  
History Of ◽  
Proven Case ◽  
Mycological Examination ◽  
The Brain

Cerebral aspergillosis is a rare cause of brain expansive lesion in AIDS patients. We report the first culture-proven case of brain abscess due to Aspergillus fumigatus in a Brazilian AIDS patient. The patient, a 26 year-old male with human immunodeficiency virus (HIV) infection and history of pulmonary tuberculosis and cerebral toxoplasmosis, had fever, cough, dyspnea, and two episodes of seizures. The brain computerized tomography (CT) showed a bi-parietal and parasagittal hypodense lesion with peripheral enhancement, and significant mass effect. There was started anti-Toxoplasma treatment. Three weeks later, the patient presented mental confusion, and a new brain CT evidenced increase in the lesion. He underwent brain biopsy, draining 10 mL of purulent material. The direct mycological examination revealed septated and hyaline hyphae. There was started amphotericin B deoxycholate. The culture of the material demonstrated presence of the Aspergillus fumigatus. The following two months, the patient was submitted to three surgeries, with insertion of drainage catheter and administration of amphotericin B intralesional. Three months after hospital admission, his neurological condition suffered discrete changes. However, he died due to intrahospital pneumonia. Brain abscess caused by Aspergillus fumigatus must be considered in the differential diagnosis of the brain expansive lesions in AIDS patients in Brazil.

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